Insights into pharmaceutical co-crystallization using coherent Raman microscopy.

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Journal of pharmaceutical sciences Pub Date : 2024-11-02 DOI:10.1016/j.xphs.2024.10.054
Alba M Arbiol Enguita, Elina Harju, Lea Wurr, Teemu Tomberg, Oona Auvinen, Leena Peltonen, Clare Strachan, Jukka Saarinen
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Abstract

Formulating active pharmaceutical ingredients (APIs) as co-crystals requires a thorough understanding of co-crystallization behavior under different process conditions. This study employs two forms of coherent Raman microscopy, narrowband coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS) with spectral focusing, to study co-crystallization via liquid-assisted ball milling. Indomethacin and nicotinamide served as the model API and co-former, and the results were compared with established analytical methods. Narrowband CARS, with univariate peak position analysis, was useful to visualize co-crystal formation, but suffered some degree of signal mixing that affected component identification. Hyperspectral SRS imaging, combined with classical least squares multivariate analysis, separated the different components with high confidence and proved to be a robust and rapid tool to qualitatively and quantitatively image co-crystallization. The coherent Raman imaging results explained divergent co-crystallization endpoints obtained with the conventional solid-state analysis methods. CARS and SRS microscopies also revealed the presence of otherwise undetected trace forms. Finally, we also demonstrated the dramatic reversal of partial co-crystal formation during milling, depending on ethanol content. Overall, the study demonstrates the added value coherent Raman microscopy can provide for analysis of co-crystallization processes.

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利用相干拉曼显微镜深入了解药物共结晶。
将活性药物成分(API)配制成共晶需要全面了解不同工艺条件下的共晶行为。本研究采用窄带相干反斯托克斯拉曼散射(CARS)和带光谱聚焦的受激拉曼散射(SRS)这两种相干拉曼显微镜形式来研究通过液体辅助球磨进行的共结晶。吲哚美辛和烟酰胺分别作为模型原料药和共成体,研究结果与已有的分析方法进行了比较。采用单变量峰位分析的窄带 CARS 有助于观察共晶体的形成,但存在一定程度的信号混合,影响了成分的识别。高光谱 SRS 成像与经典的最小二乘法多元分析相结合,以较高的置信度分离出了不同的成分,并证明是定性和定量成像共晶体的可靠而快速的工具。相干拉曼成像结果解释了传统固态分析方法得出的不同共晶终点。CARS 和 SRS 显微镜还揭示了原本未检测到的痕量形式的存在。最后,我们还展示了研磨过程中部分共晶体形成的急剧逆转,这取决于乙醇含量。总之,这项研究证明了相干拉曼显微镜在分析共晶体形成过程中所能提供的附加价值。
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来源期刊
CiteScore
7.30
自引率
13.20%
发文量
367
审稿时长
33 days
期刊介绍: The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.
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